Download FORMULATION AND EVALUATION OF SINTERED GASTRO RETENTIVE TABLETS OF GLIPIZIDE

A cademic Sciences
Internati onal Journal of Pharmacy and Pharmaceuti cal Sci ences
ISSN- 0975-1491
Vol 3, Suppl 4, 2011
Research Article
FORMULATION AND EVALUATION OF SINTERED GASTRO RETENTIVE TABLETS OF GLIPIZIDE
B. SESHAGIRI*1, DR. K. A. CHOWDARY 2, Y. DEEPTHI PRIYA3
1.
Aurobindo Pharma Limited, Hyderabad, A.P, 2. St. Ann’s College of Pharmacy, Contonment, Vizianagaram, A.P, 3. Arya College of
Pharmacy, Kandi, Sangareddy, Medak (D), A.P. Email: [email protected]
Received: 1 May 2011, Revised and Accepted: 12 June 2011
ABSTRACT
Hydrodynamically Balanced Systems (HBS) with sintering technique is an approach to increase the gastric residence time of drugs in stomach. This
system is designed for site specific oral drugs with low bulk density than gastric fluids so as to buoyant the dosage form in stomach to increase the
residence time of the drug. In the present investigation, an attempt was made to design hydrodynamically balanced drug delivery systems for
Glipizide using HPMC K4M and HPMC K15M polymers by solvent casting sintering technique. Various batches of matrix tablets of Glipizide were
prepared with varying concentrations of polymers using direct compression method which were exposed to different time periods under saturated
acetone vapour system for sintering.
The tablets so designed were evaluated for physical characteristics, drug content, floating time, floating lag time, etc. The study reveals that the
formulations of HBS of Glipizide formulated has exhibited a floating lag time of less than 5 minutes and floating time of mor e than 22 hrs. From the
In-Vitro drug release studies (USP XXIII), the matrix tablets containing HPMC K 15M, which was exposed to acetone vapors for a period of 4.5 hrs,
showed 69.17% drug release in 12 hrs and showed better control of drug release in comparison with the marketed preparation. The in-vitro release
data was treated with mathematical equations, and was concluded that Glipizide released from the tablet followed Peppas model with non-Fickian
diffusion. The results indicate that gas powered Hydrodynamically Balanced Tablets of Glipizide containing HPMC K15M provides a better option for
controlled release action and improved bioavailability.
Keywords: Gastric residence, Gas generation, Floating, Glipizide, HPMC, Release kinetics, Diffusion models.
INTRODUCTION
Oral drug delivery is the most widely utilized route of
administration among all the routes that have been explored for
systemic delivery of drugs via pharmaceutical products of different
dosage form. Oral controlled drug delivery systems provides the
continuous delivery of drugs at predictable and reproducible
kinetics for a predetermined period throughout the course of GI
transit and also the system that target the delivery of a drug to a
specific region within the GI tract for either a local or systemic
action.
Conventional oral controlled dosage forms suffer from mainly two
adversities like short gastric retention time (GRT) and unpredictable
gastric emptying time. A relatively brief GI transit time of most drug
products (8 -12 h) impedes the formulation of single daily dosage
forms. These problems can be overwhelmed by altering the gastric
emptying. Therefore it is desirable to formulate a controlled release
dosage form that gives an extended GI residence time. 1, 2
A number of approaches have been used to increase the GRT of a
dosage form in stomach by employing a variety of concepts. Various
gastro retentive techniques were used including floating, swelling,
high density and bioadhesive systems.3
Floating Drug Delivery Systems (FDDS) have a bulk density lower
than gastric fluids and thus remain buoyant in the stomach for a
prolonged period of time, without affecting the gastric emptying
rate. While the system is floating on the gastric contents, the drug is
released slowly at a desired rate from the system. This results in an
increase in the GRT and a better control of fluctuations in the plasma
drug concentrations.4
Sintering means fusion of particles or formulations of welded bonds
between particles of polymer. Controlled release oral dosage forms
were developed by sintering the polymer matrix either by exposing
to temperature above the glass transition (Tg) point of the polymer
or exposing these matrix systems to solvent vapours.5, 6. In the
present investigation, an attempt was made to use the solvent
casting method for sintering the tablets.
Glipizide is an oral anti-diabetic drug which belongs to sulfonylurea
class having narrow range of effective blood concentration and short
elimination half-life in humans and hence, it is suitable for a
sustained release form. Since the drug Glipizide has site specific
absorption in the upper part of the stomach, it was used as a model
drug to prepare gastro retention tablets.7
Hence, in the present study it was aimed to test the suitability of
using Hydroxypropyl Methylcellulose in the development of floating
drug delivery systems and for controlling the drug release from the
matrix tablets prepared by using sintering technique with the help
of solvent.
MATERIALS AND METHODS
Materials
The following materials were used in the study: Glipizide BP (Micro
Lab Ltd., Bangalore), HPMC K 4M (Sri Dev Pharmaceuticals,
Hyderabad), HPMC K15M (Aurobindo Pharma Ltd., Hyderabad),
Sodium bicarbonate, Lactose Monohydrate, Acetone (S.D. Fine Chem.
Ltd) and Magnesium Stearate (Loba Chemie). All other chemicals
used were of reagent grade.
Preparation of Matrix tablets of Glipizide
Floating matrix tablets containing Glipizide were prepared by direct
compression technique using varying concentrations of different
grades of polymers with sodium bicarbonate.
All the ingredients except magnesium stearate were blended in glass
mortar uniformly. After sufficient mixing of drug as well as other
components, magnesium stearate was added and further mixed for
additional 2-3 minutes. The tablets were compressed with 13 mm
circular punch using hydraulic press. Compression force of the
machine was adjusted to obtain the hardness in the range of 3-4 kg/cm2.
The weight of the tablets was kept constant for formulations F 1 to F12.
The compositions of all formulations were given in Table 1.
After the preparation, sintering technique was carried for the
prepared tablets. In this method, the tablets were exposed to
acetone vapors at different time intervals kept in a dessicator filled
with acetone at the bottom and equilibrated for 24 hrs for varying
time periods. The reason for selecting acetone as the solvent is due
to the partial solubility of HPMC in acetone as complete solubility
would dissolve the polymer and insolubility would not serve the
purpose of sintering.
Seshagiri et al.
Int J Pharm Pharm Sci, Vol 3, Suppl 4, 128-135
Table 1: Composition of Hydrodynamically Balanced tablets of Glipizide
Ingredients*
Glipizide
HPMC K4M
HPMC K15M
Sodium bicarbonate
Lactose
Magnesium stearate
Sintering Time (hrs)
F1
13
200
--20
70
7
--
F2
13
200
--20
70
7
1.5
F3
13
200
--20
70
7
3.0
F4
13
200
--20
70
7
4.5
F5
13
--200
20
70
7
--
F6
13
--200
20
70
7
1.5
F7
13
--200
20
70
7
3.0
F8
13
--200
20
70
7
4.5
F9
13
100
100
20
70
7
--
F10
13
100
100
20
70
7
1.5
F11
13
100
100
20
70
7
3.0
F12
13
100
100
20
70
7
4.5
*All the ingredients are in milligrams per tablet
Buoyancy / Floating Test
The buoyancy of the tablets was studied at 37±0.5° C, in simulated
gastric fluid at pH 1.2. The time between introduction of dosage
form and its buoyancy on the simulated gastric fluid and the time
during which the dosage form remain buoyant were measured. The
time taken for dosage form to emerge on surface of medium called
Floating Lag Time (FLT) or Buoyancy Lag Time (BLT) and total
duration of time by which dosage form remain buoyant is called
Total Floating Time (TFT). The buoyancy of the tablets was studied
in 0.1N HCl at 37±0.5°C.
The swelling behavior of a dosage form was measured by studying
its weight gain or water uptake. The dimensional changes could be
measured in terms of the increase in tablet diameter and/or
thickness over time. Water uptake was measured in terms of percent
weight gain, as given by the equation.
=
Data Analysis (Curve fitting analysis)11
To analyze the mechanism of the drug release rate kinetics of the
dosage form, the data obtained were plotted as:
1) Cumulative percentage drug released Vs time (In-Vitro drug
release plots)
Swelling Study 8
W
The tablet was kept inside the ring assembly and placed inside the
dissolution vessel. The speed was set at 100 rpm. 5 mL of sample
was withdrawn at predetermined time intervals for 12 hours and
same volume of fresh medium was replaced. The samples were
analyzed for drug content against 0.1N HCl as a blank at max 233
nm using UV spectrophotometer.
(Wt – Wo)
Wo
x
100
Wt = Weight of dosage form at time t
Wo = Initial weight of dosage form
Test for Content Uniformity
Glipizide tablets containing 13 mg of drug was dissolved in 100 mL
of 0.1N HCl and kept for sonication. The solution was filtered, 1mL of
filtrate was taken in 50 mL of volumetric flask and diluted up to
mark with 0.1N HCl and analyzed spectrophotometrically at 233 nm.
The concentration of Glipizide in mg/ml was obtained by using
standard calibration curve of the drug. Claimed drug content was 13
mg per tablet. Drug content studies were carried out in triplicate for
each formulation batch.
Effect of hardness on Buoyancy Lag Time (BLT) or Floating Lag
Time9
Formulation F5 was selected to study the effect of hardness on
buoyancy lag time. The tablets of batch F 5 were compressed at four
different compression pressures to get the hardness of 4 kg/cm2, 5
kg/cm2, 6 kg/cm2 and 7 kg/cm2. The tablets were evaluated for
Buoyancy Lag Time. The method followed is same as that of
Buoyancy test.
In-vitro Dissolution Study
In-vitro release studies were carried out using USP XXIII
dissolution test apparatus. 900 mL of 0.1N HCl (pH 1.2) was filled
in dissolution vessel and the temperature of the medium was set
at 37°±0.1°C. For the study ring/mesh assembly was used. The
reason was that, when paddle apparatus was used, the tablets
would rise and eventually stick to the flange of the rotating shaft
resulting in partial surface occlusion. In case of basket apparatus,
it was observed that after 5 - 7 hr the tablets had swollen to such
an extent that they were completely constricted by the radius of
the basket and completely filled the bottom of the basket. Once the
dosage form completely fills the basket, tablet was unable to swell
further and move in unimpeded fashion leading to limited drug
release. In order to overcome these drawbacks ring mesh device
was employed in the study. 10
2) Cumulative percentage drug released Vs Square root of time
(Higuchi’s plots)
3) Log cumulative percentage drug remaining Vs Time (First order
plots)
4) Log percentage drug released Vs log time (Peppas plots)
Scanning Electron
formulation
Micro
graphs
of
the
optimized
Morphological details on the specimens were determined by using
SEM models GSM 35 CF Joel Japan. Conventional SEM sample
preparation methods were applied for these studies. The samples
were dried thoroughly in vacuum dessicator before mounting on a
brass specimen studs. The samples were mounted using double
sided adhesive tape and gold palladium alloy of 120 A0 thickness
was coated on the sample using sputter coating unit in argon
ambient of 8-10 with plasma voltage about 2KV and discharge
current about 20 MA. The SEM was operated at low accelerating
voltage of about 15 KV with a load current of about 80 MA. The
condenser lens position was maintained at a constant level. Working
distance was 39 mm; the photomicrographs were recorded at 500X,
1000X, 3000X and 4000X.
Comparison with marketed product
The promising formulation was compared with marketed Glipizide
CR formulation.
RESULTS
Hydrodynamically balanced tablets of Glipizide were prepared and
evaluated for their use as gastro retentive drug delivery systems to
increase its local action and bioavailability. In the present work, total
twelve formulations were prepared and complete compositions of
all batches were shown in Table 3. The formulated tablets were then
characterized for various physico-chemical parameters.
Pre-compression Parameters
Angle of Repose (θ)
The values obtained for angle of repose for F 1, F5 and F9 formulations
are tabulated in Table 2. The values were found to be 24°.30', 26°.77'
and 25°.28'. This indicates good flow property of the powder blend.
Compressibility Index
Compressibility index values for F1, F5 and F9 formulations were
12.30, 15.67 and 15.41% respectively indicating that the powder
blends have the required flow property for direct compression.
129
Seshagiri et al.
Int J Pharm Pharm Sci, Vol 3, Suppl 4, 128-135
Post-compression Parameters
Weight Variation Test
Tablet dimensions
The percentage of weight variations for all formulations was shown
in Table 2.
The dimensions determined for formulated tablets were tabulated in
Table 2. Tablets mean thicknesses were almost uniform in all the
formulations and were found to be in the range of 5.14 mm to 5.18 mm.
The diameter of the tablet ranges between 11.02 mm to 11.21 mm.
All the tablets passed weight variation test as the % weight variation
was within the pharmacopoeial limits. The weights of all the tablets
were found to be uniform with low standard deviation values.
Table 2: Physical properties of tablets of batches F1, F5 and F9
Batch
No.
F1
F5
F9
Angle
of Repose (θ)
24°.30'
26°.77'
25°.28'
Compressibility
Index (%)
12.30
15.67
15.41
Diameter
(mm)
11.19 ± 0.04
11.20 ± 0.06
11.22 ± 0.05
Thickness (mm)
5.16 ± 0.08
5.14 ± 0.02
5.18 ± 0.02
Wt. variation
(mg)
312 ± 1.29
307 ± 1.34
311 ± 1.49
Drug Content
Uniformity (%)
98.71
97.12
99.50
Hardness test
Friability Test
The measured hardness of tablets for each batch ranges from 3.6
kg/cm2 to 4.3 kg/cm2 (Table 3). Tablet hardness was increased with
increase in the sintering time. This ensures good handling
characteristics of all batches.
The values of friability test were tabulated in Table 3. Tablets
exposed to acetone vapors for a greater period showed the least
friability as compared to the tablets that were unsintered. Therefore,
by using this technique of sintering the friability of tablets can be
reduced to a greater extent. The % friability was less than 1% in all
the formulations ensuring that the tablets were mechanically stable.
Table 3: Hardness and Friability
Parameter
Hardness
(kg/cm2)
F1
3.6 ±
0.21
F2
3.6 ±
0.20
F3
3.7 ±
0.30
F4
3.9 ±
0.06
F5
3.9 ±
0.05
F6
4.0 ±
0.07
F7
4.1 ±
0.50
F8
4.3 ±
0.42
F9
3.8 ±
0.50
F10
3.8 ±
0.04
F11
3.9 ±
0.54
F12
4.0 ±
0.12
Friability
(%)
0.63
0.41
0.38
0.20
0.28
0.24
0.18
0.04
0.48
0.38
0.31
0.12
Tablet density
To provide good floating behavior in the stomach, the density of the
device should be less than that of the gastric contents (1.004 g/cm3).
All the batches showed density below than that of gastric fluid
(1.004). The values are shown in Table 4. When the tablet contacts
test medium, tablet gets expanded (because of swellable polymers)
and there was liberation of CO2 gas (because of effervescent agent,
NaHCO3). The density decreased due to this expansion and upward
force of CO2 gas generation. This plays an important role in ensuring
the floating capability of the dosage form.
Table 4: Tablet Density, Buoyancy Lag Time and Total Floating Time
Batch No.
F1
F2
F3
F4
F5
F6
F7
F8
F9
F10
F11
F12
Tablet Density (g/cc)
0.96
0.94
0.93
0.89
0.90
0.88
0.85
0.82
0.95
0.92
0.88
0.87
Buoyancy Lag Time (minutes)
5 min 21 sec
5 min 11 sec
4 min 48 sec
4 min 05 sec
4 min 22 sec
4 min 12 sec
3 min 45 sec
3 min 14 sec
4 min 40 sec
4 min 26 sec
4 min 13 sec
4 min 07 sec
Total Floating Time (hrs)
> 20
> 20
> 20
> 20
> 24
> 24
> 24
> 24
> 22
> 22
> 22
> 22
Fig. 1: Picture depicting the floating tablet of Glipizide
130
Seshagiri et al.
Int J Pharm Pharm Sci, Vol 3, Suppl 4, 128-135
Buoyancy Study
that the batch containing only HPMC K 15M polymers showed good
Buoyancy lag time (BLT) and Total floating time (TFT). Buoyancy lag
times of the formulations were found to decrease as the time of
sintering was increased. Formulation F 8 containing HPMC K15M and
exposed to acetone vapors for 4.5 hrs showed good BLT of 3 min 14
sec and TFT greater than 24 hrs.
in Fig. 2. Buoyancy of the tablet was governed by both the swelling
of the hydrocolloid particle on surface when it contacts the gastric
fluid which in turn results in an increase in the bulk volume and the
presence of internal void space in the dry center of the tablet
(porosity). Increase in the hardness of the tablets, results in
increased buoyancy lag time which might be due to high
compression resulting in reduction of porosity of the tablet and
moreover, the compacted hydrocolloid particles on the surface of
the tablet cannot hydrate rapidly when the tablet reaches the gastric
fluid and as a result of this, the capability of the tablet to float is
significantly reduced.
On immersion in solution of 0.1N HCl with pH 1.2 at 37° C, the
tablets floated and remained buoyant without disintegration. Table
4 shows the results of Buoyancy study and Fig. 1 show Buoyancy
character of prepared tablet. From the results it can be concluded
Swelling Study
Swelling ratio describes the amount of water that is contained
within the hydrogel at equilibrium and is a function of the network
structure, hydrophilicity and ionization of the functional groups.
Swelling study was performed on F 1, F5, F9 batches for 5 hr. The
results of swelling index are given in Table 5.
From the results it was concluded that swelling increases as the time
passes because the polymer gradually absorb water due to
hydrophilicity of polymer. The outermost hydrophilic polymer
present in the tablet matrix hydrates swells and forms a gel barrier.
As the gelatinous layer progressively dissolves and/or is dispersed,
the hydration swelling release process is repeated towards new
exposed surfaces, thus maintaining the integrity of the dosage form.
Table 6: Effect of Hardness on Buoyancy Lag Time of Batch F 5
Hardness (kg/cm2)
4 kg/cm2
5 kg/cm2
6 kg/cm2
7 kg/cm2
In the present study, the higher swelling index was found for tablets
of batch F5 containing HPMC K15M having nominal viscosity of
15,000 cps. Thus, the viscosity of the polymer had major influence
on swelling process, matrix integrity as well as floating capability.
Hence from the results it can be concluded that linear relationship
exists between swelling process and viscosity of polymer.
Buoyancy Lag Time (sec)
262 sec
337 sec
431 sec
645 sec
Table 5: Swelling Index of Tablets of Batch F 1, F5 and F9
Time (hrs)
700
Swelling Index (%)
F1
F5
80
82
129
135
148
162
168
185
185
207
1
2
3
4
5
600
F9
79
130
156
172
189
500
Buoyancy Lag
Time (sec)
400
300
200
Drug Content Uniformity
100
The percentage of Glipizide content in the prepared tablets was
found to be 97.12% to 99.5%, which was within the acceptable
limits. Table 2 showed the results of drug content uniformity in each
batch.
0
1
2
3
4
Hardness (kg/cm2)
Effect of hardness on Buoyancy Lag Time
Fig. 2: Effect of hardness on Buoyancy Lag Time
The effect of hardness on buoyancy lag time for batch F 5 was studied
because it showed buoyancy lag time of 59 sec at hardness of 4
kg/cm2.
In-vitro Dissolution Study
The in-vitro drug release profiles of tablet from each batch (F 1 to F12)
were carried in 0.1N HCL having pH 1.2 for 12 hrs by using ring
mesh device. Percentage drug release from all the formulations were
shown in the Table 7 and the plot of % Cumulative drug release Vs
time (hr) was plotted and depicted as shown in Fig. 3, 4 and 5.
The results of floating lag time of tablet having hardness of 4 kg/cm2,
5 kg/cm2, 6 kg/cm2 and 7 kg/cm2 were 4 min 22 sec, 5 min 37 sec, 7
min 11 sec and 10 min 45 sec respectively as tabulated in Table 6.
The plot of floating lag time (sec) V/s hardness (kg/cm2) is depicted
Table 7: In-Vitro drug release profile of Glipizide from all formulations
Batch No.
Time (hrs)
0.3
1
2
3
4
5
6
7
8
9
10
11
12
F1
F2
% Drug Released
27
24
34
28
37
35
53
41
56
55
61
58
70
64
74
70
79
75
83
80
90
85
98
93
99
96
F3
F4
F5
F6
F7
F8
F9
F10
F11
F12
19
23
34
38
45
53
58
64
73
77
86
91
93
17
22
30
32
43
48
56
61
70
82
83
85
86
22
30
38
51
57
61
68
77
83
86
89
91
93
17
19
27
34
38
59
61
74
79
83
84
87
89
12
19
25
30
37
38
53
57
64
70
76
77
78
7
10
15
28
38
44
48
52
57
59
60
66
69
24
31
34
50
53
59
67
70
76
80
87
91
95
20
25
31
48
51
57
64
69
71
79
85
89
90
17
23
27
44
48
54
63
64
72
77
83
86
87
12
20
24
38
44
48
51
57
60
72
77
79
82
131
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Int J Pharm Pharm Sci, Vol 3, Suppl 4, 128-135
Fig. 3: In-Vitro drug release of Glipizide for F1, F2, F3 and F4 formulations exposed to acetone vapors at different time intervals
Fig. 4: In-Vitro drug release of Glipizide for F5, F6, F7 and F8 formulations exposed to acetone vapors at different time intervals
Fig. 5: In-Vitro drug release of Glipizide for F9, F10, F11 and F12 formulations exposed to acetone vapors at different time intervals
From the in-vitro dissolution data, it was found that the drug release
studies from formulations containing HPMC K 15M sintered for 1.5,
3.0 and 4.5 hrs, the cumulative percentage releases were 88.58,
77.58 and 69.17% respectively and 93.11% for unsintered tablet.
Formulations containing HPMC K 4M, sintered for 1.5, 3.0 and 4.5 hrs,
the cumulative percentage release was 96.34, 92.78 and 85.67%
respectively and 99.25% for unsintered tablets. While the
formulations containing both polymers sintered for 1.5, 3.0 and 4.5
hrs, the cumulative percentage release was 89.55, 86.96 and 82.43%
respectively and 95.05% for unsintered tablets.
132
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Int J Pharm Pharm Sci, Vol 3, Suppl 4, 128-135
Curve Fitting Analysis
The results of dissolution data was fitted to various drug release
kinetic equations. Peppas model was found to be the best fitted in all
dissolution profiles having higher correlation coefficient (r-value)
followed by Higuchi model and First order release equation. The
kinetic values obtained for different formulations are tabulated in
Table 7. Korsemeyer-Peppas model indicates that release
mechanism is not well known or more than one type of release
phenomena could be involved. 'n' value could be used to
characterize different release mechanisms and in the present study
'n' value ranges from 0.5 to 1 for all the batches. So, it was
concluded that the drug release occurred via non-Fickian diffusion,
which shows that the release from initially dry, hydrophilic glassy
polymers that swell when added to water and become rubbery show
anomalous diffusion as a result of the rearrangement of
macromolecular chains.
Table 6: Curve fitting data for all formulations
Batch
No.
F1
F2
F3
F4
F5
F6
F7
F8
F9
F10
F11
F12
First order Equation
Slope
Rate constant
(K) mg. hr-1
-0.1317
-0.303
-0.0978
-0.225
-0.0868
-0.199
-0.0725
-0.166
-0.0914
-0.210
-0.0821
-0.189
-0.0555
-0.127
-0.0415
-0.0955
-0.0897
-0.206
-0.077
-0.177
-0.0717
-0.165
-0.0588
-0.135
Regression
coefficient (r)
0.8104
0.8905
0.9264
0.9518
0.9868
0.976
0.9748
0.988
0.9305
0.972
0.9791
0.972
Higuchi’s Equation
Slope
Rate constant (K)
mg. hr-1
25.958
25.958
26.341
26.341
27.229
27.229
26.735
26.735
26.453
26.453
29.158
29.158
25.089
25.089
23.275
23.275
25.389
25.389
25.854
25.854
26.184
26.184
25.11
25.11
Stability Studies
The selected formulation (F 8) was tested for 8 weeks at the storage
conditions of 250 C and 400 C at 60 % RH and 75 % RH respectively,
were analyzed for their drug content. The residual drug contents of
formulations were found to be within the permissible limits as
shown in the Table 7.
The tablets were also subjected to IR studies to determine
compatibility of the drug with the excipients used in the tablets. The
Regression
coefficient (r)
0.9780
0.9784
0.9715
0.9553
0.9894
0.9523
0.9642
0.9792
0.9841
0.9855
0.9831
0.9794
Peppas Equation
Slope
Regression
coefficient (r)
0.5785
0.9817
0.5687
0.9919
0.607
0.9831
0.6686
0.9697
0.5631
0.9858
0.7313
0.9599
0.6975
0.9742
0.7762
0.9812
0.5845
0.9839
0.6482
0.9884
0.6082
0.9823
0.6486
0.9867
IR studies showed that there are no interactions between the drug
and polymers.
Scanning electron microscope
Fig. 6 depicts the cross section and pore formation of the gelled
matrix of a tablet after swelling in the dissolution medium. Hence, it
proves integrity of the membrane after swelling and this ensures the
flow of drug through the gelled matrix tablet is by diffusion
mechanism.
Fig. 6: Photographs Showing the Scanning Electron Microscopy of Gelled Matrix
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Table 7: Stability data of F8 formulation
Time in weeks
0
2
4
6
8
Formulation F8
Stored at 25 0C/ 60% RH
Physical Appearance
+++
+++
+++
+++
++
Stored at 40 0C/ 75% RH
Physical Appearance
+++
+++
+++
++
++
% Drug Content
97.58
96.98
97.95
96.98
95.75
% Drug Content
97.61
94.47
96.81
95.89
94.21
+++ = Same as on zero day, ++ = Slight change in colour
Comparison with Marketed Product
The promising formulation (F 8) as found by evaluation studies was
compared with marketed product Glipizide CR. The marketed
product gave 92.78% of drug release in 12 hrs of dissolution study.
In-vitro dissolution profile of marketed product in comparison to
the formulation F8 were shown graphically in Fig. 7 and showed that
the formulation F8 with 69.17% of drug release has better control
over release of drug in comparison with marketed product.
Fig. 7: Comparative drug release profiles between marketed product and F 8 formulation
DISCUSSION
In the present investigation gastric retentive system of Glipizide
were prepared with HPMC K 4M and HPMC K15M polymers.
Glipizide has site-specific absorption in the upper part of the
stomach and hence these systems are useful in the improving the
absorption of the drug. Release of the drug from the tablets
prepared with HPMC K 4M and HPMC K15M polymers was
controlled by sintering with acetone solvent method, which avoids
the thermal degradation of the drug. Hydrodynamically Balanced
Tablets of Glipizide could be formulated as an approach to
increase gastric residence time and thereby improve its
bioavailability. HPMC K4M and HPMC K15M matrix tablets of
Glipizide were prepared by direct compression technique and the
tablets were exposed to acetone vapors in a desiccator filled with
acetone at the bottom for the time intervals for a period of 1.0, 3.5
and 4.5 hrs. Formulated tablets gave satisfactory results for
various physicochemical parameters like Tablet dimensions,
Hardness, Friability, Weight variation, Tablet density, Swelling
index and Content uniformity. FT-IR studies revealed that there
are no chemical interactions between Glipizide and the polymers
used in the study. Among all the batches, tablets of batch F8
possessed quick buoyancy lag time and good total floating time.
Variation on hardness on tablet of batch F5 was found to effect the
floating lag time of the tablet as hardness increased. The
dissolution profiles for Glipizide made with HPMC K 4M and HPMC
K15M, showed that the use of these polymers permit efficient
control of the release of the drug. The observed formulation
difference in dissolution rates can be attributed to differences in
the viscosity-enhancing effect of the HPMC and also the drug:
HPMC ratio. The tablets made with lower polymer content and
lower viscosity have faster dissolution rates, thus increasing the
dissolution of drug. The effect of sintering time on the drug release
from matrix tablets was evaluated and it was found that the time
of sintering is proportional to the amount of drug release. From all
the formulations, F8 containing HPMC K15M, which is exposed to
acetone, vapors for about 4.5 hrs showed extended drug release.
The kinetics of drug release and the release mechanism from
sintered matrix tablets were ascertained and found to be Firstorder and the mechanism of drug release followed Peppa’s
diffusion model. Formulation F8 has better controlled drug release
in comparison to marketed product.
CONCLUSION
In the present study Gastro retentive delivery systems of Glipizide
were successfully developed in the form of Hydrodynamically
Balanced Tablets to improve the local action and ultimately its
bioavailability.
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